CASO 1. Xavier Matias-Guiu Hospital Universitari Arnau de Vilanova, Universitat de Lleida, IRBLLEIDA.

Transcription

1 CASO 1 Xavier Matias-Guiu Hospital Universitari Arnau de Vilanova, Universitat de Lleida, IRBLLEIDA.

2 ASSESSMENT OF PRIMARY ORIGIN IN PATIENTS WITH A PREVIOUS HISTORY OF CANCER

3 Primary Tumor T1 T5 T6 T13 T14 N T T2 T2 T2 T3 T7 T8 T8 T4 T9 T10 T11 T15 T16 T11 T12 T17 T18 Metastasis

4 Primary Tumor #1 T1 T4 T5 T8 T9 N T T2 T2 T2 T3 T6 T7 T10 N T T1 T2 T3 Primary Tumor #2

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6 54 year old woman Clinical History Small cell carcinoma of the lung. Metastatic work-up negative. A combined treatment with chemotherapy (cisplatin and VP16) and radiotherapy was administered. Prophylactic cranial irradiation. Left ovarian mass, 3 months ofter finishing treatment (two years after diagnosis)

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8 Immunohistochemistry TTF-1 positive p63 negative

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11 Immunohistochemistry TTF-1 positive p63 negative

12 Differential Diagnosis Ovarian metastasis of small cell carcinoma of the lung Primary Small cell Ovarian carcinoma (hypercalcemic or pulmonary type)

13 SMALL CELL CARCINOMA OF THE OVARY, HYPERCALCEMIC TYPE Young patients Unilateral High stage Hypercalcemia Occasional component of large cells Follicle-like structures Vimentin may be positive Bad prognosis

14 SMALL CELL CARCINOMA OF THE OVARY,PULMONARY TYPE Wide range of age of presentation (28 85) Unilateral or bilateral High stage Association with surface epithelial components (endometrioid, Brenner) (MANEC??) Similar to pulmonary SCC

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16 Primary Tumor T1 T5 T6 T13 T14 N T T2 T2 T2 T3 T7 T8 T8 T4 T9 T10 T11 T15 T16 T11 T12 T17 T18 Metastasis

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18 Diagnosis Ovarian metastasis of small cell carcinoma of the lung Concordant p53 mutation

19 A 53 year- old man with a thyroid tumor

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21 TTF-1 Calcitonin

22 Synaptophysin Chromogranin A

23 Previous hystory of bladder carcinoma

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26 Diagnosis Thyroid metastasis of Small cell carcinoma of the bladder Concordant p53 mutation

27 Clinical History 57 year old man Thyroid Follicular Carcinoma (3 cm) with two foci of anaplastic carcinoma, eight years ago. Brain Tumor, consistent with metastatic tumor unknown origin

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29 Diagnosis Thyroid Follicular Carcinoma with foci of anaplastic carcinoma. Brain metastasis from the anaplastic carcinoma component Concordant p53 mutation

30 Historia Clínica Mujer, 42 años. Múltiples nódulos pulmonares.

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32 ER PR Mamoglobin GCDF-15

33 Historia Clínica Mujer, 42 años. Múltiples nódulos pulmonares. Exploración mamaria negativa. Al cabo de unos meses, se detecta un tumor vulvar, que la paciente refiere tener desde hacia cierto tiempo

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35 CK 7 CK 20 PR mamoglobin GCDF-15 ER

36 Estudio Molecular Sequenciación- Ion Torrent, Ion AmpliSeq Cancer Hotspot Panel Ambos tumores comparten una mutación en p53 Gene Nucleotide change Protein Effect Frequency TP53 g C>T R273H Substitution - Missense 10,3%* Coverage Allele Cov Data Bases COSM10660 rs

37 Diagnóstico Adenocarcinoma vulvar de tipo mamario, con metástasis pulmonares

38 ASSESSMENT OF PRIMARY ORIGIN IN PATIENTS WITH A PREVIOUS HISTORY OF CANCER

39 CASO 1 Xavier Matias-Guiu Hospital Universitari Arnau de Vilanova, Universitat de Lleida, IRBLLEIDA.

40 CASO 2 Xavier Matias-Guiu Hospital Universitari Arnau de Vilanova, Universitat de Lleida, IRBLLEIDA.

41 78 year old woman Clinical History (1) No previous history of cancer A large peritoneal tumor (11 cm in largest diameter), radiologically consistent with GIST. Several other peritoneal tumors from 2 to 6 cm in diameter Fine-needle aspiration biopsy was performed

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45 C-KIT

46 SM Actin

47 Caldesmon

48 CD 10

49 ER

50 WT-1

51 Ki-67

52 Differential Diagnosis GIST, c-kit negative Low grade stromal sarcoma

53 Molecular Analysis c-kit wild type PDFRA wild type

54 C-KIT PDGFRA

55 Clinical History (2) A diagnosis of low-grade sarcoma was done. Removal of the mases was recommended, in order to reduce tumor mass, and also in order to obtain fresh tissue to perform RT-PCR for specific translocations of low-grade endometrial stromal sarcoma. The patient refers that she underwent histerectomy with bilateral salpingoophorectomy for benign lesions, 25 years before. No more details were provided.

56 Clinical History (3) The peritoneal tumor (11 cm in largest diameter), was removed. Several other peritoneal tumors from 2 to 6 cm in diameter were also removed. Formalin-fixed paraffin-embedded material was obtained for conventional patghological analysis Fresh-frozen tissue was obtained for RT-PCR analysis

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61 Immunohistochemistry Actin and caldesmon, positive KIT negative ER and CD 10 positive Cyclin D1 negative

62 Molecular Analysis RT-PCR with specific primers for each fusion Transcriptome sequencing to confirm the fusion

63 LOW GRADE ENDOMETRIAL STROMAL SARCOMA Specific Translocations JAZF1-SUZ12 PHF1-JAZF1 EPC1-PHF1 ZC3H7B BCOR

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66 Diagnosis Low grade endometrial stromal sarcoma (metastatic?, arising in peritoneal endometriosis?), with positive MEAF6/PHF1 fusion

67 Clinical History (3) The patient s family refers having found the pathological report of the hysterectomy and bilateral salpingoophorectomy that was performed 25 years ago. Diagnosis was endolymphatic stromal myosis, an old dessignation of low-grade stromal sarcomas Paraffin blocks were requested.

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71 CD 10

72 ER

73 Diagnosis Metastatic low grade endometrial stromal sarcoma to the peritoneum, 25 years after removal the primary uterine tumor, with positive MEAF6/PHF1 fusion

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77 LOW GRADE ENDOMETRIAL STROMAL SARCOMA Peri and postmenopausal women (> 50 years old) assymptomatic, vaginal bleeding, or abdominal mass intramural or polypoid uterine mass Prominent invasion Multiple types of differentiation overall survival ranges from 69 to 84% at 5 years, but recurrences may occur many years after initial diagnosis.

78 LOW GRADE ENDOMETRIAL STROMAL SARCOMA Mimic endometrial stromal cells of the proliferative phase Mitotic index lower than 5 M /HPF May exhibit smooth muscle, fibroxyxoid or sex-cord differentiation May contain endometrial glands Positive for CD10, ER, WT-1 Specific gene fusions: JAZF1-SUZ12, PHF1-JAZF1, EPC1- PHF1 y MEAF6-PHF1

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80 HIGH GRADE ENDOMETRIAL STROMAL SARCOMA High histologic grade, but may contain a low grade component Round cells or spindle cells that do not mimic endometrial stromal cells of the proliferative phase Mitotic index higher than 10 M /HPF High grade component is negative for CD10, ER, and positive for cyclin D1 Specific gene fusion: YWHAE-FAM22

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83 UNDIFFERENTITED ENDOMETRIAL STROMAL SARCOMA High histologic grade/undifferentiated cells, without differentiation Mitotic index higher than 10 M /HPF No Specific gene fusion

84 High grade sarcoma

85 LOW GRADE ENDOMETRIAL STROMAL SARCOMA Specific Translocations JAZF1-SUZ12 PHF1-JAZF1 EPC1-PHF1 MEAF6-PHF1 ZC3H7B BCOR

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89 Diagnosis Metastatic low grade endometrial stromal sarcoma to the peritoneum, 25 years after removal the primary uterine tumor, with positive MEAF6/PHF1 fusion

90 Take home messages Endometrial sarcomas show specific gene fusions. Their detection may be diagnostically important in cases with unusual presentation (extrauterine locations / absence of a known primary tumor) Endometrial low-grade stromal sarcomas and ovarian granulosa cell tumors may relapse many years after surgical resection of the primary tumor. Molecular diagnosis may help when there is no evidence of a primary tumor

91 Historia Clínica Paciente de 54 años de edad. Obstruccion intestinal. Carcinomatosis peritoneal

92 Alpha-inhibin + Calretinin + Keratins FOXL2 mutation

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94 Diagnóstico Metástasis peritoneal de tumor de células de la granulosa

95 Take home messages Endometrial sarcomas show specific gene fusions. Their detection may be diagnostically important in cases with unusual presentation (extrauterine locations / absence of a known primary tumor) Endometrial low-grade stromal sarcomas and ovarian granulosa cell tumors may relapse many years after surgical resection of the primary tumor. Molecular diagnosis may help when there is no evidence of a primary tumor

96 CASO 2 Xavier Matias-Guiu Hospital Universitari Arnau de Vilanova, Universitat de Lleida, IRBLLEIDA.